Discipline in Stages: Regulating CD8+ Resident Memory T Cells

Abstract

Resident memory CD8⁺ T (T_RM) cells are a lymphocyte lineage distinct from circulating memory CD8⁺ T cells. T_RM lodge within peripheral tissues and secondary lymphoid organs where they provide rapid, local protection from pathogens and control tumor growth. However, dysregulation of CD8⁺ T_RM formation and/or activation may contribute to the pathogenesis of autoimmune diseases. Intrinsic mechanisms, including transcriptional networks and inhibitory checkpoint receptors control T_RM differentiation and response. Additionally, extrinsic stimuli such as cytokines, cognate antigen, fatty acids, and damage signals regulate T_RM formation, maintenance, and expansion. In this review, we will summarize knowledge of CD8⁺ T_RM generation and highlight mechanisms that regulate the persistence and responses of heterogeneous T_RM populations in different tissues and distinct microenvironments.

Keywords: T cell differentiation; microenvironment; recall response; tissue resident memory T cell; transcriptional regulation.